Ukraine's HIV epidemic, fueled primarily among opioid-dependent people who inject drugs (PWIDs), remains volatile despite gains achieved elsewhere. PWIDs account for ~70% of cumulative and >56% of new HIV infections. Despite Ukraine's HIV epidemic transition toward a generalized epidemic, empiric and mathematical modeling suggest that medication-assisted therapy (MAT) is the most effective and cost-effective approach to reverse this trend. MAT is associated with reduced HIV transmission and improved HIV treatment outcomes including engagement in care and antiretroviral medication access and adherence. Though MAT is free and capacity has increased from 120 to ~8,000 sub sized slots since 2004, <2% of PWIDs receive it. MAT scale-up is complex, poorly understood and has been fraught with low entry and high attrition. By 2011, only ~6100 slots remain filled - a number that has not increased appreciably in 12 months. Corrective interventions that facilitate MAT entry and retention are therefore crucial for HIV prevention and treatment efforts in Ukraine. We propose to improve MAT scale-up and build regional capacity in two distinct ways. In addition to examining client- and program-level facilitators and barriers to MAT, we will train and support Ukrainian experts in implementing an evidence-based and sustainable intervention, the Network for the Improvement of Addiction Treatment (NIATx) Model of Rapid Change Cycle, to improve MAT entry and retention. We will then evaluate the impact of the NIATx approach on MAT programs across Ukraine, using a pre/post intervention design to assess programmatic changes that promote MAT entry and retention. Second, we will create a new healthcare delivery model by integrating extended release naltrexone (XR-NTX) into HIV clinical care settings as a means to increase MAT access among HIV+ PWIDs. Administered only once-monthly, XR-NTX is a newly available and safe non-narcotic MAT that does not require narcological registration or have to be dispensed solely in licensed centers. Using implementation science techniques, we will examine both HIV (linkage to and retention in HIV care, initiation of and adherence with antiretroviral therapy) and substance abuse (time to opioid relapse, percent of days opioid free, retention on XR-NTX) treatment outcomes among an observational cohort of HIV+ PWIDs. The research and dissemination plan, consistent with PEPFAR's goals, expands sustainable treatment and prevention strategies and strengthens government partner relations by convening stakeholder meetings (e.g. Alliance Ukraine, Narcology and AIDS Center Directors, Ministry of Health, CDC, USAID, WHO, UNODC, Global Fund, Clinton Foundation, NGOs, etc) to facilitate NIATx implementation. By introducing evidence-based strategies and newly available medications that can forge new frontiers in HIV prevention and treatment, this project also builds local capacity and expertise in these innovative areas. Ukrainian HIV/AIDS programs also become better integrated and aligned with broader global health goals to improve health systems and maximize treatment capacity for multiple related and overlapping medical and psychiatric co-morbidities. PUBLIC HEALTH RELEVANCE: Ukraine's explosive HIV epidemic, the most devastating in Europe, is primarily fueled by people who inject drugs (PWIDs). Despite medication-assisted therapy (MAT) being the most effective and cost-effective approach to reversing the epidemic, MAT scale-up in Ukraine has been hindered by poor MAT entry and retention. The proposed research identifies the barriers and facilitators to MAT, introduces an evidence-based intervention (NIATx) to promote sustainable MAT scale-up as well as innovatively introduces a new form of MAT, extended release naltrexone, to be integrated into HIV clinical care settings. This project meets PEPFAR's objectives to: 1) transition from an emergency response to HIV/AIDS to promotion of sustainable country programs; 2) strengthen partner government capacity to lead the response to this epidemic and other health demands; 3) expand prevention, care, and treatment in concentrated and generalized epidemics; 4) integrate and coordinate HIV/AIDS programs with broader global health and development programs to maximize impact on health systems; and 5) invest in innovation and operations research to evaluate existing programs, improve service delivery and maximize program outcomes.